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From the Genomics Research Centre (Drs. Griffiths, Nyholt, and Lea), Griffith University-Gold Coast, Queensland, Australia; The National Hospital for Neurology and Neurosurgery (Dr. Goadsby), London, England; and the Institute of Neurological Sciences (Dr. Brimage), Prince of Wales Hospital, Randwick, Australia.
Address correspondence and reprint requests to Dr. Lyn R. Griffiths, Genomics Research Centre, School of Health Science, Griffith University, Gold Coast, PMB 50 GCMC, Qld. Australia, 9726.
Migraine is a frequent familial disorder that, in common with most multifactorial disorders, has an unknown etiology. The authors identified several families with multiple individuals affected by typical migraine using a single set of diagnostic criteria and studied these families for cosegregation between the disorder and markers on chromosome 19, the location of a mutation that causes a rare form of familial hemiplegic migraine (FHM). One large tested family showed both cosegregation and significant allele sharing for markers situated within or adjacent to the FHM locus. Multipoint GENEHUNTER results indicated significant excess allele sharing across a 12.6-cM region containing the FHM Ca2+ channel gene, CACNL1A4 (maximum nonparametric linkage Z score = 6.64, p = 0.0026), with a maximum parametric lod score of 1.92 obtained for a (CAG)n triplet repeat polymorphism situated in exon 47 of this gene. The CAG expansion did not, however, appear to be the cause of migraine in this pedigree. Other tested families showed neither cosegregation nor excess allele sharing to chromosome 19 markers. HOMOG analysis indicated heterogeneity, generating a maximum HLOD score of 3.6. It was concluded that Chr19 mutations either in the CACNL1A4 gene or a closely linked gene are implicated in some pedigrees with familial typical migraine, and that the disorder is genetically heterogeneous.
Supported by funding from Griffith University-Gold Coast and the Australia Government Employees Medical Research Fund. The work of Dr. Peter Brimage was supported by a Headache Fellowship provided by Glaxo Wellcome, and Dr. Peter Goadsby is a Wellcome Senior Research Fellow.
Received September 9, 1997. Accepted in final form December 16, 1997.
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